title: Interaction of insulin-enhancing vanadium compounds with human serum holo-transferrin.
abstract: The interaction of VO(2+) ion and four insulin-enhancing compounds, [VO(ma)2], [VO(dhp)2], [VO(acac)2], and cis-[VO(pic)2(H2O)], where Hma, Hdhp, Hacac, and Hpic are maltol, 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, acetylacetone, and picolinic acid, with holo-transferrin (holo-hTf) was studied through the combined application of electron paramagnetic resonance (EPR) and density functional theory (DFT) methods. Since in holo-hTf all of the specific binding sites of transferrin are saturated by Fe(3+) ions, VO(2+) can interact with surface sites (here named sites C), probably via the coordination of His-N, Asp-COO(-), and Glu-COO(-) donors. In the ternary systems with the insulin-enhancing compounds, mixed species are observed with Hma, Hdhp, and Hpic with the formation of VOL2(holo-hTf), explained through the interaction of cis-[VOL2(H2O)] (L = ma, dhp) or cis-[VOL2(OH)](-) (L = pic) with an accessible His residue that replaces the monodentate H2O or OH(-) ligand. The residues of His-289, His-349, His-473, and His-606 seem the most probable candidates for the complexation of the cis-VOL2 moiety. The lack of a ternary complex with Hacac was attributed to the square-pyramidal structure of [VO(acac)2], which does not possess equatorial sites that can be replaced by the surface His-N. Since holo-transferrin is recognized by the transferrin receptor, the formation of ternary complexes between VO(2+) ion, a ligand L(-), and holo-hTf may be a way to transport vanadium compounds inside the cells.
authors.affiliation: Istituto CNR di Chimica Biomolecolare , Trav. La Crucca 3, I-07040 Sassari, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Sanna
authors.forename: Giovanni
authors.initials: G
authors.lastname: Micera
authors.forename: Eugenio
authors.initials: E
authors.lastname: Garribba
mesh_terms: D006801:Humans; D007328:Insulin / Q000097:blood / Q000737:chemistry*; D015394:Molecular Structure; D011789:Quantum Theory; D014168:Transferrin / Q000737:chemistry*; D017968:Vanadium Compounds / Q000097:blood / Q000737:chemistry*
chemical_list: D007328:Insulin; D014168:Transferrin; D017968:Vanadium Compounds